An efficient domino Sonogashira/double carbopalladation/C-H-activation reaction leading to fluorescent polycyclic aromatic hydrocarbons

Article abstract of DOI:10.3987/COM-14-S(K)39

A facile synthesis of fluorescent polycyclic aromatic hydrocarbons through a highly productive palladium-catalyzed fourfold domino Sonogashira/double carbopalladation/C-H-activation process was developed.

Full text of DOI:10.3987/COM-14-S(K)39

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
An Efficient Domino Sonogashira/Double
Carbopalladation/C–H Activation Reaction Leading To
Fluoresecent Polycyclic Aromatic Hydrocarbons
Lutz F. Tietze* and Christoph Eichhorst
Institut für Organische und Biomolekulare Chemie
Georg-August-Universität Göttingen
Supporting Information
General methods
Experimental methods: All air-sensitive reactions were performed under an argon atmosphere in
flame-dried flasks and the reactants were introduced by syringe or transfer cannula. All solvents were
dried by standard methods and the reagents obtained from commercial sources were used without
further purification. Thin-layer chromatography was performed on precoated silica gel plates (SIL
G/UV254, Machery-Nagel GmbH & Co. Kg). Silica gel 60 (0.032–0.064 mm, Merck) was used for
column chromatography.
NMR spectroscopy: NMR spectra were recorded with a Varian Mercury-300, Unity-300, Inova-500
and Inova-600 spectrometer and a Bruker AMX-300 spectrometer in CDCl3; chemical shifts are given
in ppm relative to tetramethylsilane (TMS), coupling constants J in Hertz. The solvent signals were
used as references and the chemical shifts converted to the TMS scale. The multiplicities of first order
were assigned as: s (singlet), sbr (broad singlet), d (doublet), t (triplet), q (quartet), p (pentet), dd
(doublet of doublets), etc. Signals of higher orders were assigned as m (multiplet) respectively mC
(centered multiplet).
IR spectroscopy: IR spectra were recorded with a JASCO FT/IR-4100 spectrometer. All substances
were applied neat on an ATR unit.
UV spectroscopy: UV spectra were recorded with a JASCO V-630 spectrometer.
Mass spectrometry: ESI-MS and ESI-HRMS spectra were recorded with a Bruker Daltronik Apex IV,
EI-MS and EI-HRMS spectra were recorded with a Thermo Finnigan MAT 95.
The following abbreviations were used: aq. (aqueous), DMF (dimethyl formamide), DMSO (dimethyl
sulfoxide), EtOAc (ethyl acetate), MTBE (methyl tertbutyl ether), PE (petroleum ether, bp = 40–
60 °C), r.t. (room temperature), sat. (saturated).
1

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
1-Iodo-2-naphthol (8)1
A solution of H2SO4 (5.5 mL, 10 g, 104 mmol, 1.5 equiv.) in MeOH (200 mL) was charged with 2-
naphthol 7 (10.0 g, 69.4 mmol, 1.00 equiv.), KI (11.5 g, 69.4 mmol, 1.00 equiv.) and 30% aq. H2O2
solution (37.4 mL, 139 mmol, 2.00 equiv.) at 0 °C and stirred at this temperature for 1 h. After
addition of sat. aq. NaHSO3 solution (200 mL) and H2O (100 mL) the mixture was extracted with
CH2Cl2 (300 mL), the organic layer was washed with H2O (300 mL), dried over Na2SO4, filtered and
the solvent was removed in vacuo. Column chromatography (n-pentane/CH2Cl2 5:1) yielded iodide 8
as a yellow solid (13.5 g, 50.0 mmol, 72 %).
TLC: Rf = 0.25 (n-pentane/CH2Cl2, 5:1).
UV/Vis (CH3CN): λmax (nm) (lg ε) = 231 (4.772), 282 (3.744), 294 (3.673), 324 (3.408), 334 (3.476).
IR (ATR): ῦ (cm-1) = 3233, 1621, 1599, 1494, 1344, 1206, 806, 742.
1H-NMR (300 MHz, CDCl3): δ (ppm) = 5.77 (s, 1 H, OH), 7.24 (d, J = 8.9 Hz, 1 H, 3-H), 7.36 (ddd,
J = 8.1, 6.9, 1.1 Hz, 1 H, 5-H), 7.53 (ddd, J = 8.4, 6.9, 1.3 Hz, 1 H, 6-H), 7.69–7.75 (m, 2 H, 7-H, 8-H)
7.91 (dd, J = 8.5, 0.9 Hz, 1 H, 4-H).
13C-NMR (126 MHz, CDCl3): δ (ppm) = 86.2 (C-1), 116.4 (C-3), 124.2 (C-6), 128.2 (C-5), 128.3 (C-
7), 129.7 (C-4a), 130.2 (C-8), 130.6 (C-4), 134.8 (C-8a), 153.7 (C-2).
MS (EI): m/z = 143.0 (25) [M-I]+, 270.0 (100) [M]+.
HRMS (EI): m/z = found: 269.9533, calcd.: 269.9542 [M]+.
C10H7IO (270.07).
1 For original procedure see: T. Kometani et al, J. Org. Chem. 1985, 50, 5384–5387.
Experimental Data from: T. Hungerland, Dissertation, Georg-August-Universität, Göttingen, 2013; M. A.
Düfert, Dissertation, Georg-August-Universität, Göttingen, 2010.
2

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
1-Iodo-2-(4-nitrophenoxy)naphthalene (1a)2
A mixture of 1-iodo-2-naphthol 8 (5.00 g, 18.5 mmol, 1.00 equiv.) and K2CO3 (7.67 g, 55.5 mmol,
3.00 equiv.) in DMSO (50 mL) was stirred at 95 °C for 15 min. 4-Fluoronitrobenzene 9 (1.96 mL,
2.61 g, 18.5 mmol, 1.00 equiv.) was added and the reaction mixture was stirred at 95 °C for 24 h.
After the addition of H2O (200 mL) the mixture was extracted with MTBE (4 × 200 mL), the
combined organic layers were dried over Na2SO4, filtered and the solvent was removed in vacuo.
Recrystallization from n-hexane (300 mL) and CH2Cl2 (100 mL) yielded biarylic ether 1a as a brown
solid (5.69 g, 14.5 mmol, 78 %).
TLC: Rf = 0.19 (n-pentane/CH2Cl2, 5:1).
UV/Vis (CH3CN): λmax (nm) (lg ε) = 228 (4.686), 291 (4.245).
IR (ATR): ῦ (cm-1) = 1583, 1504, 1484, 1331, 1237, 1108, 842, 798, 746.
1H-NMR (300 MHz, CDCl3): δ (ppm) = 6.96–7.01 (m, 2 H, 2’-H, 6’-H), 7.21 (d, J = 8.7 Hz, 1 H, 3-
H), 7.56 (t, J = 7.5 Hz, 1 H, 6-H), 7.64 (t, J = 7.7 Hz, 1 H, 7-H), 7.85 (d, J = 8.7 Hz, 1 H, 5-H), 7.90
(d, J = 8.7 Hz, 1 H, 4-H), 7.85 (d, J = 8.7 Hz, 1 H, 5-H).
13C-NMR (126 MHz, CDCl3): δ (ppm) = 94.1 (C-1), 116.6 (C-2’, C-6’), 120.3 (C-3), 126.0 (C-3’, C-
5’), 126.6 (C-6), 128.4 (C-5), 128.6 (C-7), 131.2 (C-4), 131.9 (C-4a), 132.0 (C-8), 135.7 (C-8a), 142.9
(C-4’), 152.6 (C-2), 162.4 (C-1’).
MS (EI): m/z = 218.1 (43) [M-I-NO2]+, 263.1 (6) [M-I]+, 391.0 (100) [M]+.
HRMS (EI): m/z = found: 390.9689, calcd.: 390.9705 [M]+.
C16H10INO3 (391.16).
2 Original procedure and experimental data from: T. Hungerland, Dissertation, Georg-August-Universität,
Göttingen, 2013.
3

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
1-Methoxy-2-(2-nitrophenoxy)benzene (13)3
A mixture of 2-methoxyphenol (1.80 mL, 2.00 g, 16.1 mmol, 1.00 equiv.), 2-fluoronitrobenzene
(1.70 mL, 2.27 g, 16.1 mmol, 1.00 equiv.) and K2CO3 (4.45 g, 32.2 mmol, 2.00 equiv.) in DMSO
(40 mL) was stirred at 95 °C for 20 h. After cooling to r.t. the mixture was treated with H2O (100 mL)
and the insoluble parts were filtered off and kept, as they contained the final product. The filtrate was
extracted with MTBE (3 × 100 mL). The combined organic extracts were washed with brine
(200 mL), dried over Na2SO4, filtered and the solvent was removed in vacuo to yield biarylic ether 13
as a yellow oil (3.96 g, quant.) with little impurities.
TLC: Rf = 0.35 (n-pentane/EtOAc, 10:1).
UV/Vis (CH3CN): λmax (nm) (lg ε) = 194 (4.7202), 264 (3.7487), 319 (3.4631).
IR (ATR): ῦ (cm-1) = 1606, 1584, 1523, 1496, 1480, 1471, 1455, 1439, 1349, 1305, 1263, 1231, 1197,
1175, 1163, 1147, 1111, 1089, 1043, 1018, 883, 846, 801, 770, 746, 738, 694, 665.
1H-NMR (600 MHz, CDCl3): δ (ppm) = 3.75 (s, 3 H, OCH3), 6.80 (dd, J = 8.5, 1.2 Hz, 1 H), 6.94 (td,
J = 7.7, 1.4 Hz, 1 H), 6.99 (dd, J = 8.2, 1.4 Hz, 1 H), 7.06 (dd, J = 8.0, 1.7 Hz, 1 H), 7.08 (td, J = 7.9,
1.2 Hz, 1 H), 7.18 (td, J = 7.8, 1.6 Hz, 1 H), 7.39 (ddd, J = 8.7, 7.3, 1.7 Hz, 1 H) 7.92 (dd, J = 8.2, 1.7
Hz, 1 H).
13C-NMR (126 MHz, CDCl3): δ (ppm) = 55.9 (OCH3), 113.2, 118.1, 121.3, 121.8, 122.0, 125.6,
126.3, 133.9, 140.0, 143.3, 151.3, 151.7.
MS (ESI): m/z (%) = 246.1 (100) [M+H]+, 263.1 (94) [M+Na]+, 268.1 (92) [M+Na]+.
HRMS (ESI): m/z = found: 246.0763, calcd.: 246.0761 [M+H]+.
C13H11NO4 (245.23).
3 For original procedure see: J. A. De la Fuente, J. Med. Chem. 2003, 46, 5208–5221.
4